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- W2739570349 abstract "Evidence over the years has highlighted that intracellular redox status plays a critical role in determining cell fate. To date, we have shown that a pro-oxidant milieu, specifically a mild elevation of intracellular superoxide, promotes cancer cell survival and chemoresistance. To that end, we demonstrated in vitro that elevated superoxide, upon silencing of superoxide dismutase (SOD1), resulted in sustained phosphorylation of Bcl-2 at serine 70, thereby stabilizing its anti-apoptotic activity. These findings were corroborated by the abundance of Serine 70 Bcl2-phosphorylation and low SOD1 expression in lysates of patients with aggressive lymphomas and/or disease with poor prognosis. In addition to the anti-apoptotic protein Bcl-2, the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB)- mediated signaling was also shown to be modulated by intracellular redox milieu. As constitutive activation of NF-κB has been reported in various human tumors, which is often associated with malignant progression and chemotherapeutic resistance, here we set out to investigate whether a pro-oxidant environment, specifically the upregulation of intracellular superoxide, was associated with the induction of NF-κB transcriptional activity. Indeed, we demonstrate that elevated intracellular superoxide via the pharmacological inhibition and genetic silencing of SOD1 results in enhanced activation of canonical NF-κB signalling. This is accompanied by increased p65 nuclear localization and transcription of NF-κB regulated genes, which potentially confer survival advantages to tumour cells upon chemotherapeutic treatments. Considering the association between NF-kB activation, chronic inflammation and the process of carcinogenesis, these preliminary data provide a novel mechanism of activation of this master transcriptional factor with potential therapeutic implications. Citation Format: Michelle Y. Yee, Stephen J. Chong, Shazib Pervaiz. The oncogenic activity of a pro-oxidant intracellular milieu is associated with redox dependent activation of NF-kB [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 440. doi:10.1158/1538-7445.AM2017-440" @default.
- W2739570349 created "2017-08-08" @default.
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- W2739570349 date "2017-07-01" @default.
- W2739570349 modified "2023-09-25" @default.
- W2739570349 title "Abstract 440: The oncogenic activity of a pro-oxidant intracellular milieu is associated with redox dependent activation of NF-kB" @default.
- W2739570349 doi "https://doi.org/10.1158/1538-7445.am2017-440" @default.
- W2739570349 hasPublicationYear "2017" @default.
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